by Jonathon Sullivan MD, PhD
”[A]t present there is absolutely no solid evidence that strength training—or any other exercise or dietary program—will substantially prolong our life spans. But the preponderance of the scientific evidence, flawed as it is, strongly indicates that we can change the trajectory of decline. We can recover functional years that would otherwise have been lost.”
For some time now, in the course of my duties as an emergency physician, I’ve had strange thoughts at the bedside of some of my patients. I’ll approach a patient who has come to be treated for chronic pain, fatigue, elevated blood pressure, shortness of breath, or a blood sugar that’s out of control. I find myself confronted by a very overweight, deconditioned 52 year-old, going on 70, with battered joints, atrophic muscles, no physiologic reserve, an inability to get off the gurney without groaning and wheezing, and a grim future. When I work them up, I find no medical emergency, just what I have come to call “diatensionolesity”—type II diabetes, hypertension, a screwed-up blood-lipid profile, and obesity.
And I think to myself: If I could get you under the bar, I could change your life.
Then I give them a lecture about their weight and their smoking, write a prescription for painkillers, blood pressure medicine, diuretics or an oral hypoglycemic, and send them back to their grim future. These immediate interventions are necessary, but what I really want to do, as a physician and a person, is to alter that future, to help them recover some of their youthful vigor, to reverse the atrophy and degeneration of their sick bodies. I want to make them stronger, or at least show them that it’s possible to be stronger, and how to do it. I want to write a prescription for squats.
I think I have found a fountain of youth, and it flows out of a barbell.
I have both a personal and professional interest in aging. My personal interest is easy to understand: I’m getting older. I just turned 51. My joints are creakier, my hair is graying rapidly, and it seems like every week I need a stronger prescription for my reading glasses. My glands don’t squirt like they used to. My metabolism, left to its own devices, would rather turn calories into fat and ear hair than hard muscle and bone. I work hard to keep my mind active and learning, because while I can keep adding synapses to my brain, the number of neurons in there will only continue to fall. I’m over the hill. Now the only question is how steep the slope is on my side of the mountain.
My professional interest in aging may also seem obvious: I take care of sick people for a living, and older people tend to get sick more easily, and succumb to illness more readily. But my interest goes beyond the clinical.
Since 1995, I have been involved in cerebral ischemia research. This means that I investigate what happens to the brain when blood flow is interrupted, as happens in stroke or during cardiac arrest.  My focus is on molecular mechanisms that lead to brain cell death or survival. I’m not a particularly gifted or lucky or influential scientist. I’m just an obscure, poorly-funded ER doc doing part-time research in a basement lab, grinding away at my tiny corner of a huge problem: what happens when the most complex object in the known universe gets sick, and how do we fix it? In the course of this quixotic endeavor, I have learned a lot about how cells decide to die.
That’s right. Most of the time, cells decide to die. It’s not a passive process, but rather the culmination of an elaborate biomolecular self-destruct program called apoptosis or programmed cell death. [2, 3] Apoptosis is critical to advanced, multicellular life forms. Without it, embryonic development would be a disaster. Viral infections would spread like wildfire if cells weren’t programmed to sacrifice themselves for the greater good when compromised. And apoptosis is one of the body’s primary defenses against malignant transformation and cancer.
Apoptosis is horribly complex in the particulars, but the big picture isn’t hard to sketch out. There are two basic pathways: extrinsic and intrinsic. In extrinsic apoptosis, another cell or tissue sends a death signal, a chemical message which is picked up by the target cell and tells it to die. In the intrinsic process, a stressor causes the cell’s power plants, the mitochondria, to spill a protein called cytochrome c into the cytoplasm. Think of a leaky reactor—bad news. When cytochrome c oozes out of the mitochondria, it triggers a complex series of events that lead to apoptosis. In both intrinsic and extrinsic patterns, the terminal phase of apoptosis is carried out by proteases and nucleases—protein enzymes that cut up other proteins or DNA. These enzymes take the cell apart in an orderly fashion and clean up the mess.
At some point during apoptosis, the cell will become unrecoverable. It will be, in a word, dead. When the cellular organelles start to shrink up and disappear, there is little hope for the cell. And once a cell has started to cut up its DNA, it has blown its own brains out. Game over. However, because apoptosis is not a passive falling-apart, but a molecular program, one that has to be signaled, triggered, activated and executed, it can be modulated. Up to a point, apoptosis can be inhibited or reversed, and the most effective way to do so is through growth factor signaling. 
Growth factors are peptide hormones like human growth hormone (HGH), insulin, insulin-like growth factors (IGFs), endothelial-derived growth factor (EDGF) and nerve growth factor (NGF), among many others. Like anabolic steroids, they induce a trophic effect. However, unlike steroids, peptide growth factors act through membrane receptors on the cell surface, activating a cascade of internal signals that promote growth.
But growth factors don’t just promote growth—they promote cellular survival.
For example, you can subject cultured cells to any number of noxious stimuli that will not kill cells
outright, but will cause them to snuff themselves. Such stimuli include hypoxia, radiation, chemicals
like ceramide or arachidonate, certain types of viral infection, or overwhelming concentrations of
calcium or free radicals, to name a few. The cells will promptly activate their self-destruct programs,
shrivel up and die. However, you can slow down or arrest the apoptosis program by administering a
growth factor, such as insulin or IGF-1, to the culture. As a result of observations like these, growth
factors are under intense scrutiny for their potential to treat a number of stubborn and devastating
degenerative diseases, including stroke. 
December 3-6 : Bullets & Bourbon
December 6 Training Camp (The Squat) : Baltimore, MD
December 6 Training Camp (Press & Bench Press) : New York, NY
December 11-13 Starting Strength Seminar : Wichita Falls, TX
January 9 Training Camp (Squat, Press, Deadlift) : Brisbane, Australia
January 10 Training Camp (Squat, Press, Deadlift) : Brisbane, Australia
January 15-17 Starting Strength Seminar : Los Angeles, CA
January 16 Training Camp (Squat, Press, Deadlift) : Sydney, Australia
January 17 Training Camp (Squat, Press, Deadlift) : Sydney, Australia
January 23 Training Camp (The Squat) : Lansing, MI